In a study presented today at the American Diabetes Association’s 68th Scientific Sessions, a team led by Rohit N. Kulkarni, M.D., Ph.D., Investigator in the Joslin Section on Cellular and Molecular Physiology and Assistant Professor of Medicine at Harvard Medical School, showed that mice lacking insulin receptors in their beta cells had problems in the processing of insulin leading to excess, unprocessed levels of the hormone. Unprocessed insulin is unable to properly control glucose levels in the body.
“This is the first time that anyone has shown this,” he said.
“One of the early problems you see in patients who have not yet developed type 2 diabetes is an increase in unprocessed insulin circulating throughout the body,” Kulkarni said. “Nobody has understood how or why this happens or what it means.”
High circulating levels of unprocessed insulin and insulin resistance, a condition in which normal amounts of insulin are inadequate to produce a normal insulin response, are both known to be early indicators of type 2 diabetes. According to Kulkarni, this study provides evidence for a link between these two indicators.
It is possible that insulin resistance affects beta cells causing them to begin producing unprocessed insulin very early in the disease process, he added.
The finding is expected to prompt further research into ways to protect beta cells from developing the defects that cause the production of unprocessed insulin.
At the same time, the large increase in unprocessed insulin may be directly or indirectly leading to what is known as endoplasmic reticulum (ER) stress, another inhibitor of beta cell insulin processing, he said. Insulin resistance and ER stress both appear to be linked to the development of type 2 diabetes, he noted.
This talk is one of 87 presentations to be delivered by Joslin scientists at the ADA’s Scientific Sessions, Friday, June 6, through Tuesday, June 10 at the Moscone Convention Center in San Francisco, CA. The session, “Metabolic and Hormonal Regulation of Islet Function,” is scheduled for Sunday, June 8 from 4:15 – 6:15 p.m. PDT. [Abstract Number 215-OR: “Insulin Signaling Regulates Insulin Processing in Pancreatic Beta-Cells”]About Joslin Diabetes Center
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